Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase.

Published

Journal Article

The predominant functional adenylyl cyclases normally expressed in cardiac tissue and coupled to beta-adrenergic receptors are inhibited by micromolar Ca(2+) concentration. To modify the overall balance of activities, we have generated transgenic mice expressing the Ca(2+)-stimulatable adenylyl cyclase type 8 (AC8) specifically in the heart. AC activity is increased by at least 7-fold in heart membranes from transgenic animals and is stimulated by Ca(2+) in the same range of concentration that inhibits the endogenous activity. Moreover, the in vivo basal protein kinase A activity was augmented 4-fold. Overexpression of AC8 in the heart has no detrimental consequences on global cardiac function. Basal heart rate and contractile function, measured by noninvasive echocardiography, were unchanged. In contrast, on release of parasympathetic tone, the intrinsic contractility is heightened and unresponsive to further beta-adrenergic receptor stimulation. AC8 transgenic mice thus represent an original model to investigate the relative influence of Ca(2+) and cAMP on cardiac function within a phenotype of enhanced cardiac contractility and relaxation.

Full Text

Duke Authors

Cited Authors

  • Lipskaia, L; Defer, N; Esposito, G; Hajar, I; Garel, MC; Rockman, HA; Hanoune, J

Published Date

  • April 14, 2000

Published In

Volume / Issue

  • 86 / 7

Start / End Page

  • 795 - 801

PubMed ID

  • 10764414

Pubmed Central ID

  • 10764414

Electronic International Standard Serial Number (EISSN)

  • 1524-4571

Digital Object Identifier (DOI)

  • 10.1161/01.res.86.7.795

Language

  • eng

Conference Location

  • United States